Each year more than 500 million people contract malaria and between 2-3 million children die from the disease. Over 40 percent of the world's population lives in malaria endemic regions and with the globalization of the world's economy and travel, people from malaria free countries are increasingly exposed to the disease. The malaria parasite is rapidly becoming resistant to current drugs and there is little activity of new drug discovery in the major pharmaceutical companies. Vaccines have been tried but with little success to date. The world is in desperate need for new, safe and effective anti-malarial drugs. The focus of our work is targeting the apicoplast - a malarial organelle of chloroplast origin. We have preliminary data supporting our hypothesis that chloroplast poisons kill the parasite. The goal of this Phase I work is to provide the necessary data for proof of principle that: 1) the chloroplast-derived apicoplast is an important target for anti-malarial drug development; and 2) the chloroplast poisons are candidates for advanced drug testing. We will evaluate 3 classes of such herbicides for in vitro anti-malarial activity, demonstrate novelty of action, test for activity in resistant malarial phenotypes and test our lead drug - Atrazine in two in vivo models of anti-malarial activity. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE